GREENS – Eating your greens alters your genes

Eating your greens alters your genes

CONSIDER the Brussels sprout: small, unassuming and ostensibly good for you. This is no mere side dish. A landmark study suggests that this dinky member of the cabbage family – along with rice, broccoli and possibly all the plants you eat – changes the behaviour of your genes in ways that are new to science.

In what is the strongest evidence yet that the genetic material in food survives digestion and circulates through the body, fragments of plant RNA have been found swimming in the bloodstreams of people and cows. What’s more the study by Chen-Yu Zhang of Nanjing University in China and his colleagues shows that some of these plant RNAs muffle gene expression and raise cholesterol levels in mice. The discovery opens up a new way to turn food into medicine: we may be able to design plants that change our genes for the better.

The genetic material in question is microRNA – tiny strands of RNA between 19 and 24 "letters" or nucleotides long. It is found in almost all cells with a nucleus and travels from cell to cell in the blood. Zhang and his colleagues wondered whether all the miRNA strands in our blood are made by our cells – or whether some comes from our food instead.

To begin, the team drew blood from 31 healthy Chinese men and women, and also from cows. They treated the samples with sodium periodate, an oxidising agent that modifies mammalian miRNA so that it cannot be sequenced. Crucially, it leaves the plant versions untouched. Zhang found some 30 known plant miRNAs floating in the blood of the people and cows.

Two miRNAs were present in particularly high concentrations: MIR168a and MIR156a, which we will call 168a and 156a. They are abundant in rice and members of the Brassicaceae family, including the Brussels sprout, broccoli, cabbage and cauliflower. Surprisingly, Zhang found 168a and 156a in the livers, small intestines and lungs of mice. Given the prominence of rice in the Chinese diet – coupled with the fact that cooking does not destroy the plant miRNAs – Zhang concluded that those in the human blood samples came from food.

That plant miRNA survives digestion and circulates through the body was surprising enough. But Zhang wanted to know whether plant miRNA remains functional in animal blood.

Like a genetic volume control, miRNA muffles or amplifies gene expression by binding to strands of messenger RNA and preventing enzymes from translating the strands into a protein. To find out if 168a tweaks gene expression in animals, Zhang’s team searched the human, rat and mice genomes for sequences that complemented 168a. They found around 50 genes that 168a might turn up or down, including the gene for LDLRAP1, a liver protein that removes "bad cholesterol" from the blood.

In a series of experiments, Zhang and the team found that not only does 168a survive in animal cells, it can also change gene expression. First, Zhang added 168a to a dish of human intestinal cells. The cells packaged the 168a into tiny bubbles and released them. Zhang poured these bubbles onto mammalian liver cells, which soon began producing unusually low levels of LDLRAP1.

Then Zhang fed mice raw rice or injected them with 168a, and found that levels of this protein dropped and levels of cholesterol rose. When he injected the mice with a genetic sequence designed to inactivate 168a, levels of the cholesterol-removing protein did not drop.

Together, the evidence suggests that, in mice at least, 168a from rice survives digestion, inhibits production of a protein and boosts cholesterol levels in the blood. Put simply, a plant miRNA is capable of raising cholesterol levels in mice (Cell Research, DOI: 10.1038/cr.2011.158).

Zhang is unsure how the miRNAs escape unscathed from the caustic soup of digestive fluids and enzymes in the gut. But substantial research suggests that not all genetic matter from food dissolves in the stomach and intestines. For instance, an essential photosynthesis gene found in soya bean leaves turned up in the intestines, liver and spleen of mice fed the leaves. And it was recently revealed that the hypnotically green sea slug Elysia chloroticasteals genes for photosynthesis from the algae it eats. Researchers also discovered that the bacteria in Japanese people’s guts have sponged up genes from ocean bacteria that linger on seaweed.

Even if RNA or DNA does not pass unscathed from food to eater, food can change gene expression in other ways. For example, cosmetics researchers recently suggested that a pill containing a mix of food extracts can influence our genes and boost collagen production in the skin, reducing the appearance of wrinkles (New Scientist, 24 September, p 10).

If Zhang’s findings are replicated, we may discover that our blood is swimming with RNA from all kinds of plants. To date, all investigation of this possibility has been motivated by concerns that genes from genetically modified crops could harm health (see "Let’s talk about GM crops"). But the new study opens the possibility of designing diets and plants with therapeutic effects.

"You can bet this will create an absolute flurry of research activity" as scientists race to discover how genetic information in our food changes our health, says Ed Stellwag of East Carolina University in Greenville.

Peter Waterhouse of the University of Sydney, Australia, sees the potential for engineering medicinal plants but adds that for now this remains unchartered territory – mostly. Zhang is investigating whether miRNAs in a Chinese herb can knock out the influenza virus, but remains tight-lipped about the results.

"This will expand our idea of nutrients by including miRNA as functional component of food," says Moon-Suhn Ryu at the University of Florida in Gainesville. "This is going to introduce a new field of research, especially in nutritional science – it’s such a novel concept."